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Adrenergic Antagonist (BB) Toxicity

By Stephen Thornton, MD


β-adrenergic antagonists (beta-blockers) (BBs) are commonly used for treatment of hypertension, coronary artery disease, and tachydysrhythmias. β-adrenergic antagonists has also been used to treat congestive heart failure, glaucoma, migraine headaches, benign essential tremor, panic attacks, stage fright, and hyperthyroidism. The number of exposures reported nationally to poison centers has doubled in the past decade. Propranolol accounts for a disproportionate number of poisonings, likely due to its increased toxicity compared to other BBs and its use in patients with anxiety and stress.

Case presentation

A 65 year-old woman presented to the emergency department 3 hours after a suicidal ingestion of her metoprolol. Her heart rate was 35 beats per minute and her blood pressure was 80/40 mm Hg. The patient received intravenous glucagon 1 mg with no improvement in her hemodynamics. A second dose of intravenous glucagons 5 mg was administered. The patient’s heart rate improved to 50 beats per minute and her blood pressure increased to 90/50 mm Hg.


  1. What is the pathophysiology of BB toxicity?
  2. What are the clinical presentations of BB toxicity?
  3. What are the treatment options for BB toxicity?


β-adrenergic antagonists antagonize the chronotropic and inotropic response to catecholamines at the cardiac β-adrenergic receptors. BBs decrease inotropy through interference with the pathways involving cAMP. β-agonists bind to Gs proteins that activate adenyl cyclase, leading to the increase of intracellular production of cAMP. Increased cAMP levels activate protein kinase A, resulting in phosphorylation of myocyte proteins such as L-type calcium channels, phospholamban, ryanidine receptors, and troponin. The phosphorylation of L-type calcium channels increases cardiac contractility. BB produces negative chronotropic effect through decreased SA node function.

Clinical presentation

The cardiac presentation of β-adrenergic antagonist toxicity is an extension of the therapeutic effects. Symptoms of toxicity typically occur within 2 hours of ingestion of immediate-release products. Hypotension and bradycardia are common features of BB overdose. Hypotension occurs through the negative inotropic effect. Decreased SA node function results in sinus bradycardia. Impaired AV conduction can lead to varying AV blocks. Severe BB toxicity may result in asystole. Hypoglycemia may occur, and is more common in children with BB toxicity. Bronchospasm is relatively uncommon after BB overdose.

Propranolol is a unique BB with increased toxicity due to its lipophilic and membrane-stabilizing properties. In addition to hypotension and bradycardia, prolonged QRS interval, seizures, and coma may also occur.

Sotalol causes prolongation of the QT interval via potassium channel blockage. Toxicity can be delayed and prolonged, and may result in ventricular dysrhythmias, including torsades de pointes.


β-adrenergic antagonist toxicity should be considered in patients who present with hypotension and bradycardia. The differential diagnosis should include toxicity from calcium channel blockers, α-2 agonists, and digoxin. All patients with an intentional overdose of a BB should have a 12 lead EKG and continuous cardiac monitoring with pulse oximetry performed. Laboratory testing should include serum electrolytes, serum glucose concentration, BUN, creatinine, and digoxin level. Serum concentrations of BBs are not readily available for routine clinic use.


Initially management for β-adrenergic antagonist toxicity includes airway management, and continuous cardiac monitoring. GI decontamination should be considered in individuals without a contraindication such as altered mental status or vomiting. Activated charcoal should be considered if a patient presents within 1 hour of ingestion. Whole bowel irrigation with polyethylene glycol should be considered in patients who have ingested sustained release preparations. In patients with propranolol overdose and widened QRS, sodium bicarbonate should be administered. Convulsions from propranolol overdose may be treated with benzodiazepines and sodium bicarbonate.


The initial treatment for bradycardia is atropine. In patients who fail to respond to atropine, glucagon 5-10 mg IV bolus should be administered, followed by 5-10 mg/hr intravenous infusion. Glucagon works by increasing adenyl cyclase activity independent of beta-adrenergic receptor binding. Glucagon may cause vomiting with a risk of aspiration.

Ventricular pacing may be considered in refractory cases however it may not be successful. Frequently there is failure to capture in BB toxicity. Pacing may increase the heart rate in some patients without increase in cardiac output or blood pressure.


The initial management of hypotension is IV fluids and glucagon. In patients who fail to respond to IV fluids and glucagon, calcium may be given to treat the hypotension. The starting dose of calcium gluconate 10% solution is 3 gm IV in an adult. Repeated doses may be given until the serum calcium reaches 13-15 mg/dL. In pediatric patients, the initial dose of calcium gluconate is 60 mg/kg up to 3 gm. Calcium chloride provides three times more calcium than calcium gluconate. Calcium chloride is preferentially administered through central line as extravasation of calcium chloride into the tissues may lead to skin necrosis.

High dose insulin combined with glucose therapy to maintain euglycemia is beneficial in patients with BB poisoning. Insulin increases myocardial utilization of carbohydrates, which is the favored source of energy during stress. The increased glucose uptake results in increased myocardial contractility. High-dose insulin, euglycemia (HIE) therapy is safe and simple to administer with appropriate monitoring of glucose and potassium. HIE is thus recommended in patients who do not respond to fluids, atropine, and glucagon. Therapy usually begins with a bolus of 1 unit/kg of regular insulin with 0.5g/kg of dextrose. If the initial blood glucose in >400 mg/dL, the dextrose bolus is not necessary. The theoretical advantage of administration an initial insulin bolus is to rapidly saturate insulin receptors to enhance the physiological response. This is followed by an infusion of regular insulin at 0.5 to 1 unit/kg/h. A continuous infusion of dextrose at 0.5 g/kg/h should also follow a bolus. The blood glucose should be monitored every 30 minutes until stable and then every 1 to 2 hours subsequently thereafter.

Intravenous fat emulsion (IFE) is a newer antidote that may be utilized in the poisoning of lipid-soluble β-adrenergic antagonists such as propranolol, penbutolol, timolol, metoprolol, carvedilol, and labetalol. Although the exact mechanism of action is unknown, the IFE is hypothesized to reduce the toxicity by soaking up lipid-soluble xenobiotics and removing them from the site of toxicity. The recommended dose is 20% IFE at 1.5 ml/kg bolus followed by 0.25 ml/kg/min or 15 ml/kg/h intravenous infusion for 30 to 60 minutes.

Patients who do not respond to the aforementioned therapies usually require a catecholamine infusion. The choice of catecholamine is controversial. Epinephrine intravenous infusion at 1 mcg/min and titrate upwards as needed, or norepinephrine intravenous infusion at 4-8 mcg/min and titrate upwards as needed, may be effective.

Extracorporeal removal is ineffective for the lipid-soluble BBs due to their large volume of distribution. Hemodialysis is effective in removal water-soluble BB such as atenolol and acebutolol; however, may be technically difficult in a hypotensive patient. Intra-aortic balloon pump or extracorporeal membrane oxygenation (ECMO) may be considered in patients who are refractory to previous interventions.

Toxicity from BB poisoning almost always occurs within 6 hours of ingestion. Therefore patients may be discharged from medical care after a period of observation of 6-8 hours if they remain asymptomatic with normal vital signs and a normal ECG. Exceptions to this include sustained-release products, or sotolol, where delayed toxicity has been observed and an observation period of 24 hours is recommended.

Discussion of case questions and key points

  1. What is the pathophysiology of BB toxicity?
    BB decrease inotropy through interference with Gs protein, which activates adenyl cyclase, increases intracellular production of cAMP, activates protein kinase A, phosphorylates of myocyte proteins and increases inotropy.
  2. What are the clinical presentations of BB toxicity?
    The clinical presentations of BB toxicity are hypotension and bradycardia. Hypoglycemia may occur. AV conduction blocks, prolonged QRS and QT intervals, and asystole may occur in severe poisonings.
  3. What are the treatment options for BB toxicity?
    Treatment options for BB toxicity include glucagon, calcium, high-dose insulin/euglycemia, intravenous fat emulsion, and vasopressors. Intra-aortic balloon pump or extracorporeal membrane oxygenation may be considered in refractory cases.